chr4-68816683-T-C

Variant names:

• chr4-68816683-T-C
• NM_001075.6:c.664T>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001075.6(UGT2B10):​c.664T>C​(p.Trp222Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,628 control chromosomes in the GnomAD database, with no homozygous occurrence. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. W222S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: UGT2B10 NM_001075.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.408
• Publications: 0 publications found

Genes affected

UGT2B10 (HGNC:12544): (UDP glucuronosyltransferase family 2 member B10) Predicted to be involved in lipid metabolic process. Predicted to be located in endoplasmic reticulum membrane. Predicted to be integral component of membrane. Predicted to be active in intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001075.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UGT2B10	NM_001075.6	MANE Select	c.664T>C	p.Trp222Arg	missense	Exon 1 of 6	NP_001066.1	P36537-1
	UGT2B10	NM_001144767.3		c.466+198T>C		intron	N/A	NP_001138239.1	P36537-2
	UGT2B10	NM_001290091.2		c.-27+511T>C		intron	N/A	NP_001277020.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UGT2B10	ENST00000265403.12	TSL:1 MANE Select	c.664T>C	p.Trp222Arg	missense	Exon 1 of 6	ENSP00000265403.7	P36537-1
	UGT2B10	ENST00000458688.2	TSL:2	c.466+198T>C		intron	N/A	ENSP00000413420.2	P36537-2
	UGT2B10	ENST00000878267.1		c.664T>C	p.Trp222Arg	missense	Exon 1 of 6	ENSP00000548326.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459628 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 726088

African (AFR) AF: 0.00 AC: 0 AN: 33350

American (AMR) AF: 0.00 AC: 0 AN: 44480

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25960

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39590

South Asian (SAS) AF: 0.00 AC: 0 AN: 86026

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53318

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5744

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110886

Other (OTH) AF: 0.00 AC: 0 AN: 60274

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.46
BayesDel_addAF	Benign	-0.080	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	21
DANN	Benign	0.76
DEOGEN2	Benign	0.099	T
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.32	T
M_CAP	Benign	0.0056	T
MetaRNN	Uncertain	0.48	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Pathogenic	3.2	M
PhyloP100		0.41
PrimateAI	Benign	0.30	T
PROVEAN	Pathogenic	-11	D
REVEL	Benign	0.17
Sift	Uncertain	0.015	D
Sift4G	Benign	0.37	T
Polyphen		0.86	P
Vest4		0.37
MutPred		0.61		Gain of methylation at W222 (P = 0.0667)
MVP		0.42
MPC		0.029
ClinPred		0.89	D
GERP RS		1.4
Varity_R		0.26
gMVP		0.65
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr4-69682401;